Hereditary photoreceptor degeneration is a group of blinding retinal diseases with diverse genetic origins. We propose to perform functional studies of several proteins known or postulated to have essential roles in photoreceptors. Emphasis is placed on the connecting cilium and the mammalian equivalent of a periciliary ridge complex, and their roles in membrane protein transport to the outer segment and disc morphogenesis. The proposed research will study RPGR, RPGRIP and Tubby-like proteins, hypothesized to function in the above processes. Our approaches are based on analyses of in vivo genetic models complemented by in vitro cell biological studies. The proposed efforts should contribute to our understanding of disease mechanisms underlying photoreceptor degeneration, and advance our knowledge concerning important and lesser understood aspects of photoreceptor cell biology.